Selective Aminofunctionalization of 1,3-Dienes and Aryl Cyclopropanes Enabled by Copper Catalysis

Abstract

Within organic chemistry, transition metal catalysis has emerged as an invaluable tool for the development of novel reaction systems. Amongst these methods, transition metal catalyzed amination strategies are of the utmost importance due to the ubiquity of nitrogen in bioactive compounds of interest, ligands, and catalysts. Given the high degree of molecular complexity seen in most nitrogen-containing compounds, difunctionalization reactions that are able to install multiple functionalities in fewer steps are highly desirable. Simple alkenes are widely available as starting materials for difunctionalization and work well under transition metal catalysis to afford 1,2-difunctionalized products. However, novel methods utilizing other accessible starting materials are required to expand difunctionalization reaction capabilities to other substitution patterns and motifs.Conjugated 1,3-dienes offer access to a wide variety of isomeric products to deliver a range of aminated motifs based on regio-, site-, and geometric selectivity. Despite this, diene 1,4-aminofunctionalizaiton remains underdeveloped and demands further study. Based on this gap in the field, a copper-catalyzed 1,4-aminohydroxylation reaction has been developed using O-benzoylhydroxylamines as an electrophilic source of aliphatic amines. The reaction system is amenable to a wide variety of carbonyl-containing 1,3-diene substrates and has been successfully expanded to deliver exclusive 1,4-aminothiolated products from thioamide-containing 1,3-dienes. Cyclopropanes represent another class of difunctionalization substrate that remains underdeveloped. The difunctionalization of cyclopropanes by ring-opening reactions serves as an access point to 1,3-functionalized motifs, a substitution pattern inaccessible by alkene or diene functionalization. Utilizing the unique reactivity of cyclopropanes for ring-opening difunctionalization, an enantioselective copper-catalyzed 1,3-aminoalkynylation of non-activated aryl cyclopropanes has been established.